In recent years, it has become possible to obtain cells having pluripotency similar to embryonic stem cells (hereafter referred to as ES cells) by selecting cells expressing Fbxo15 gene from somatic cells such as fibroblasts in which Oct3/4 gene, Sox2 gene, Klf4 gene, and c-myc gene have been introduced and expressed (International Patent Application Publication No. WO2007/069666; Takahashi K, and Yamanaka S. (2006) Cell 126:663-676). It is considered that if pluripotent stem cells derived from somatic cells thus obtained are used in regenerative medicine, the cells of a patient can become transplanted to the patient himself so that rejection problems would be smaller than when ES cells are used.
While somatic cell-derived pluripotent stem cells (hereafter referred to as induced pluripotent stem cells, or iPS cells) established by using Fbxo15 gene as a marker were closely similar to embryonic stem cells in terms of cell morphology, proliferation ability, differentiation ability etc., they were different from ES cells in some characteristics such as gene expression and DNA methylation patterns. Then, the cells were selected by using the expression of the Nanog gene as a marker, and iPS cells having pluripotency more similar to ES cells were established (Okita K, Ichisaka T, and Yamanaka S. (2007) Nature 448:313-317).
Later, iPS cells were isolated using changes in cell morphology as a marker, instead of the expression of Fbxo15 gene or Nanog gene (Meissner A, Wernig M, and Jaenisch R. (2007). Nat Biotechnol 25:1177-1181). iPS cells were also established by using N-myc instead of c-myc (Blelloch R, Venere M, Yen J, Ramalho-Santos M. (2007) Cell Stem Cell 1:245-247). Further, in mice as well as in humans, iPS cells were established by introducing the three genes of Oct3/4, Sox2 and Klf4, without using c-myc gene (Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, and Yamanaka S. (2008). Nat Biotechnol 26:101-106; Wernig M, Meissner A, Cassady J P, and Jaenisch R. (2008) Cell Stem Cell 2:10-12). In addition, iPS cells were established from hepatocytes and gastric epithelial cells, besides fibroblasts (Aoi T, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, and Yamanaka S. (2008) Science (Feb. 14, 2008) (published online).).
Meanwhile, there has also been a growing body of studies using human cells. Human iPS cells were established by introducing into fibroblasts four genes of Oct3/4, Sox2, Nanog, and lin28 (Yu J, Vodyanik M A, Smuga-Otto K, Antosiewicz-Bourget J, Frane J L, Tian S, Nie J, Jonsdottir G A, Ruotti V, Stewart R, Slukvin I I, and Thomson J A. (2007) Science 318:1917-1920) the same combination of genes (i.e. Oct3/4 gene, Sox2 gene, Klf4 gene, and c-myc gene) as used for establishment of mouse iPS cells (Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, and Yamanaka S. (2007) Cell 131:861-872).
Since iPS cells can be produced using cells derived from a patient to be treated, artificial organs and the like which are escaped from rejection are expected to be produced by using iPS cells in the field of regenerative medicine.